Project Summary/Abstract: Taste receptor cells detect chemicals in our food and communicate this information to the nerve fibers innervating them. Our goal is to understand the structural and functional relationship between taste receptor cells and innervating neurons. Because taste receptor cells undergo continuous renewal and must constantly attract and connect to nerve fibers even in the adult, some mechanism exists to control this process. Since the neurotrophin BDNF controls initial innervation of taste buds and is present in adult taste receptor cells, it may have this role. BDNF also can function as a neuromodulator regulating function, so it is certainly possible that BDNF can regulate both innervation and/or function of adult taste buds. Here we are testing the hypothesis that BDNF signaling through its receptor, TrkB, regulates both the structural and functional connections between taste receptor cells and ganglion neurons. The proposed studies combine sparse cell genetic labeling with 3-dimensional analysis of the taste bud and electrophysiology, in mice where TrkB-signaling can be blocked using a combination of chemical and genetic approaches to: 1) determine the identity and connectivity of BDNF expressing taste receptor cells, 2) determine the role of BDNF-TrkB-signaling in maintaining this connectivity, and 3) determine if BDNF-TrkB signaling regulates taste function. Together, these experiments will determine how specific taste receptor cells (BDNF-expressing) become innervated by a subset of taste ganglion neurons (TrkB-expressing) during taste cell renewal and will determine if BDNF-TrkB-signaling is an important gustatory system neuromodulator of this pathway.